This page is taking too long to load.

Geoffrey Beene Global NeuroDiscovery Challenge

Total Votes Received = 6300

Following rigorous scientific review, three projects have made it to the final round of voting. Now it's your turn to decide! Your VOTE will help determine which researcher will be awarded an extra $50,000 to seek answers for gender based differences in Alzheimer’s disease.

Voting is open to the public. Only one vote is allowed per participant per day during the duration of the award voting.

Voting will open on November 1 at 7:00am and close November 5 at midnight EST.

Winner of the 21CBT Award will be announced online and live on November 7, 2013 at the New York Academy of Science’s Global CEO Initiative on Alzheimer’s Disease Summit.

Video and details for Male/Female Differences in Aging Brains in a Gene For Ubiquitin-Specific Peptidase 9 (USP9) as a Possible Cause for Increased Incidence of Alzheimer’s Disease in Older Women

Video and details for SCARB1 as a Mediator Of Male/Female Differences in Alzheimer’s Disease

Video and details for Male/Female Differences in Alzheimer’s Disease Have Unique Changes in Cellular Networks

SCARB1 as a Mediator Of Male/Female Differences in Alzheimer’s Disease

ABSTRACT: To pursue mechanisms by which gender may modify Alzheimer’s Disease (AD) risk, we re-analyzed whole-transcriptome cerebral cortex gene expression data in unaffected individuals in function of their gender as well as in AD patients and observed significant similarities between the gene expression signature observed in elderly women (vs men) and AD patients (vs unaffected controls), suggesting that some physiological processes are modified in elderly unaffected women brain in a manner that could prime for AD. To identify potential causal factors underlying the observed changed, we proceeded to a differential co-expression correlation network analysis of the gender and AD transcriptomic changes and identified SCARB1 – a cell surface receptor involved in cholesterol management and already know to have gender-specific functions - as a core regulatory mediator of the joint effect of gender and LOAD. Confirming this unbiased genome-wide first stage, genetic analyses revealed that a common polymorphism within SCARB1 impact LOAD age-of-onset in a gender-specific fashion in several patients cohorts. These data thus point at SCARB1 as a gene mediating the increased LOAD risk observed in women. It thus makes it a therapeutic target of choice and more globally suggest an involvement of cholesterol in the increase AD incidence observed in women, and suggests potential interest in cholesterol-lowering drugs such as statins to reduce AD risks in women. Remarkably, a systematic unbiased approach identified a gene involved in cholesterol and cardio-vascular functions that thus make a very strong candidate at the light of our current knowledge of both AD risk factors and gender-dependent diseases.

You're in!

ABSTRACT: Alzheimer’s Disease (AD) affects nearly five million people annually in the US, nearly two-thirds of whom are women. While numerous studies have attempted to identify genetic and environmental causes for the disease, little progress has been made in understanding the mechanisms that drive its development and progression. Gene expression profiling data captures a snapshot of the molecular state of the cell and can provide a window on the processes that are active in normal and disease states. Here we are proposing to use a systems-biology approach to investigate sexual dimorphism in AD by modeling the transcriptional networks that are activated in normal and disease tissue in both males and females. Our preliminary findings suggest that there are sex-specific differences in brain tissue transcriptional networks that converge as AD develops and progresses. We are proposing to further validate our preliminary findings in additional data sets in order to identify sex-specific biomarkers, and to inform potential sex-specific therapeutic interventions that will address the unique aspects of AD in females and males.

You're in!

Male/Female Differences in Aging Brains in a Gene For Ubiquitin-Specific Peptidase 9 (USP9) as a Possible Cause for Increased Incidence of Alzheimer’s Disease in Older Women

ABSTRACT: Recent studies on aging of the human brain show that age-related gene expression changes may display significant differences between the genders. One of the genes with the largest differences between male and female expression levels across multiple brain regions during adulthood is the Y-chromosomal ubiquitin-specific peptidase 9 (USP9Y; the differences are not compensated by the female homologue USP9X). Interestingly, in post-mortem brain samples from male Alzheimer’s disease (AD) patients a significant down-regulation of USP9Y is observed as compared to unaffected male controls, while no significant changes are detected for USP9X. Studying the protein interaction network reveals associations of USP9Y with microtubule-associated protein tau (MAPT), known for the formation of neuroﬁbrillary tangles in AD, and with SIRT1, previously linked with aging/longevity and AD. USP9X/Y is also a known regulator of the TGF-beta/BMP signaling pathway and deubiquitinates monoubiquitinated SMAD4, opposing the inhibitory activity of E3 ubiquitin-protein ligase TRIM33 and resulting in downstream TGF-beta activation. Since previous studies showed neuroprotective effects for TGF-beta activation in multiple in-vitro and in-vivo models of neurodegeneration, and fly AD models affirm an involvement of USP9X/Y in MAPT regulation, the combined observations suggest that age-dependent higher USP9X/Y levels in males may contribute to previously observed gender differences in AD.